582 research outputs found
A well-conserved Plasmodium falciparum var gene shows an unusual stage-specific transcript pattern
No full textThe var multicopy gene family encodes Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variant antigens, which, through their ability to adhere to a variety of host receptors, are thought to be important virulence factors. The predominant expression of a single cytoadherent PfEMP1 type on an infected red blood cell, and the switching between different PfEMP1 types to evade host protective antibody responses, are processes thought to be controlled at the transcriptional level. Contradictory data have been published on the timing of var gene transcription. Reverse transcription-polymerase chain reaction (RT-PCR) data suggested that transcription of the predominant var gene occurs in the later (pigmented trophozoite) stages, whereas Northern blot data indicated such transcripts only in early (ring) stages. We investigated this discrepancy by Northern blot, with probes covering a diverse var gene repertoire. We confirm that almost all var transcript types were detected only in ring stages. However, one type, the well-conserved varCSA transcript, was present constitutively in different laboratory parasites and does not appear to undergo antigenic variation. Although varCSA has been shown to encode a chondroitin sulphate A (CSA)-binding PfEMP1, we find that the presence of full-length varCSA transcripts does not correlate with the CSA-binding phenotype
Plasmodium falciparum:Rosettes do not protect merozoites from invasion-inhibitory antibodies
No full textRosetting is a parasite adhesion phenotype associated with severe malaria in African children. Why parasites form rosettes is unknown, although enhanced invasion or immune evasion have been suggested as possible functions. Previous work showed that rosetting does not enhance parasite invasion under standard in vitro conditions. We hypothesised that rosetting might promote invasion in the presence of host invasion-inhibitory antibodies, by allowing merozoites direct entry into the erythrocytes in the rosette and so minimising exposure to plasma antibodies. We therefore investigated whether rosetting influences invasion in the presence of invasion-inhibitory antibodies to MSP-1. We found no difference in invasion rates between isogenic rosetting and non-rosetting lines from two parasite strains, R29 and TM284, in the presence of MSP-1 antibodies (P = 0.62 and P = 0.63, Student's t test, TM284 and R29, respectively). These results do not support the hypothesis that rosettes protect merozoites from inhibitory antibodies during invasion. The biological function of rosetting remains unknown
Virulence of malaria is associated with differential expression of Plasmodium falciparum var gene subgroups in a case-control study
No full textPlasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a major pathogenicity factor in falciparum malaria that mediates cytoadherence. PfEMP1 is encoded by approximately 60 var genes per haploid genome. Most var genes are grouped into 3 subgroups: A, B, and C. Evidence is emerging that the specific expression of these subgroups has clinical significance. Using field samples from children from Papua New Guinea with severe, mild, and asymptomatic malaria, we compared proportions of transcripts of var groups, as determined by quantitative polymerase chain reaction. We found a significantly higher proportion of var group B transcripts in children with clinical malaria (mild and severe), whereas a large proportion of var group C transcripts was found in asymptomatic children. These data from naturally infected children clearly show that major differences exist in var gene expression between parasites causing clinical disease and those causing asymptomatic infections. Furthermore, parasites forming rosettes showed a significant up-regulation of var group A transcripts
Identification of Plasmodium falciparum var1CSA and var2CSA domains that bind IgM natural antibodies
No full textMalaria in pregnancy is responsible for maternal anaemia, low-birth-weight babies and infant deaths. Plasmodium falciparum infected erythrocytes are thought to cause placental pathology by adhering to host receptors such as chondroitin sulphate A (CSA). CSA binding infected erythrocytes also bind IgM natural antibodies from normal human serum, a process that may facilitate placental adhesion or promote immune evasion. The parasite ligands that mediate placental adhesion are thought to be members of the variant erythrocyte surface antigen family P. falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by the var genes. Two var gene sub-families, var1CSA and var2CSA, have been identified as parasite CSA binding ligands and are leading candidates for a vaccine to prevent pregnancy-associated malaria. We investigated whether these two var gene subfamilies implicated in CSA binding are also the molecules responsible for IgM natural antibody binding. By heterologous expression of domains in COS-7 cells, we found that both var1CSA and var2CSA PfEMP1 variants bound IgM, and in both cases the binding region was a DBL epsilon domain occurring proximal to the membrane. None of the domains from a control non-IgM-binding parasite (R29) bound IgM when expressed in COS-7 cells. These results show that PfEMP1 is a parasite ligand for non-immune IgM and are the first demonstration of a specific adhesive function for PfEMP1 epsilon type domains
A comprehensive approach to health literacy: validating the All Aspects of Health Literacy Scale in a respresentative sample of Arabic-speaking adult Syrian refugees
No full textMASTER OF SCIENCE (2017), McMaster University, Hamilton ON (Department of Global Health)
TITLE: A comprehensive approach to health literacy: validating the all aspects of health literacy scale (AAHLS) in a representative sample of Arabic-speaking adult Syrian refugees
AUTHOR: Raafia Siddiqui, BSc Hons. (York University, 2014)
SUPERVISOR: Dr. K. Bruce Newbold
NUMBER OF PAGES: vii, 92The purpose of this study is to quantify current health literacy levels amongst a segment of the Syrian refugee population in Canada by translating and validating an existing comprehensive health literacy assessment tool, the All Aspects of Health Literacy Scale (AAHLS) into Arabic. This study (1) determined functional, communicative and critical health literacy levels amongst Syrian refugees. Functional and critical health literacy was comparatively low but respondents seemed able to effectively communicate with their providers and access supports to read and fill in health documents. Significant correlates of low health literacy were presence of long-term health conditions and place of origin (country versus refugee camp). This study also validated the AAHLS in Arabic-speaking Syrian refugees, with a Cronbach’s alpha of 0.67 for the overall scale and 0.63 for health literacy items. The overall scale had high content validity. The feasibility of this instrument as a self-administered screening tool in clinical or community settings was demonstrated with a high response rate of 0.86.ThesisMaster of Science (MSc)Health literacy looks at an individual's ability to read, understand and interpret health information and ultimately use it to exert greater control over their health. The purpose of this study is to understand the factors that influence health literacy levels amongst a segment of the Syrian refugee population in Canada by translating and validating an existing comprehensive health literacy assessment tool, the All Aspects of Health Literacy Scale (AAHLS) into Arabic. This study (1) determined functional (reading and filling in health documents), communicative (speaking to health providers) and critical health (assessing the relevance and appropriateness of health information) literacy levels amongst Syrian refugees. Functional and critical health literacy was comparatively low but respondents seemed able to effectively communicate with their providers and access supports to read and fill in health documents. Low health literacy was associated with having a long-term health conditions and staying in a refugee camp. This study found the translated AAHLS to be reliable, with a Cronbach’s alpha of 0.67 for the overall scale and 0.63 for health literacy items. The overall scale had high content validity. The feasibility of this instrument as a self-administered screening tool in clinical or community settings was demonstrated with a high response rate of 0.86
A Comparison of the Predictors of Heart Health Among Immigrants and Native-Born Canadians
No full textWith over 18% of the Canadian population born outside of Canada, the health of immigrants is an important concern. Heart health is of particular importance because heart disease is the leading cause of death among men and women in Canada. Using data from the National Population Health Survey (NPHS), the purpose of this thesis is to first establish whether immigrants to Canada have lower rates of coronary heart disease (CHD), and high blood pressure (HBP) than native-born Canadians, and second to determine the lifestyle and psychosocial factors that predict heart health and compare them between immigrants and native-born Canadians. Regression and survival analyses of the NPHS data indicate that lifestyle and psychosocial risk factors such as smoking status, body mass index, alcohol consumption and depression affect immigrants and native-born Canadians similarly. Immigration variables such as length of time in the host country and country of origin are significant risk factors for HBP, however, not in the incidence of CHD. Immigrants were more likely to have HBP than native-born Canadians. However, immigrants have a significantly lower incidence of CHD than native-born Canadians. Native-born Canadians are at a higher risk of heart disease at a younger age than immigrants. These results suggest that there must be other factors relating to immigration affecting the heart health of immigrants. Due to the complexity and high incidence of heart disease in Canada, it may never be possible to ascertain all of the risk factors for heart disease. However, this study has identified several key risk factors and has excluded other variables as possible risk factors. The risk factors identified in this study can form the basis for the development of heart health programs to target all Canadians-both native-and foreign-born.ThesisMaster of Arts (MA
CR1 Knops blood group alleles are not associated with severe malaria in the Gambia
No full textThe Knops blood group antigen erythrocyte polymorphisms have been associated with reduced falciparum malaria-based in vitro rosette formation (putative malaria virulence factor). Having previously identified single-nucleotide polymorphisms (SNPs) in the human complement receptor 1 (CR1/CD35) gene underlying the Knops antithetical antigens Sl1/Sl2 and McC(a)/McC(b), we have now performed genotype comparisons to test associations between these two molecular variants and severe malaria in West African children living in the Gambia. While SNPs associated with Sl:2 and McC(b+) were equally distributed among malaria-infected children with severe malaria and control children not infected with malaria parasites, high allele frequencies for Sl 2 (0.800, 1,365/1,706) and McC(b) (0.385, 658/1706) were observed. Further, when compared to the Sl 1/McC(a) allele observed in all populations, the African Sl 2/McC(b) allele appears to have evolved as a result of positive selection (modified Nei-Gojobori test Ka-Ks/s.e.=1.77, P-valu
Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
No full textThis ESMO Clinical Practice Guidelines provide updated state-of-the-art recommendations on management of thyroid cancer (diagnosis, treatment and follow-up), compiled by a multidisciplinary author panel and accompanied by level of evidence and grade of recommendation, depending on the strength of supporting data and magnitude of benefit from particular intervention
The role of Plasmodium falciparum var genes in malaria in pregnancy
No full textSequestration of Plasmodium falciparum-infected erythrocytes in the placenta is responsible for many of the harmful effects of malaria during pregnancy. Sequestration occurs as a result of parasite adhesion molecules expressed on the surface of infected erythrocytes binding to host receptors in the placenta such as chondroitin sulphate A (CSA). Identification of the parasite ligand(s) responsible for placental adhesion could lead to the development of a vaccine to induce antibodies to prevent placental sequestration. Such a vaccine would reduce the maternal anaemia and infant deaths that are associated with malaria in pregnancy. Current research indicates that the parasite ligands mediating placental adhesion may be members of the P. falciparum variant surface antigen family PfEMP1, encoded by var genes. Two relatively well-conserved subfamilies of var genes have been implicated in placental adhesion, however, their role remains controversial. This review examines the evidence for and against the involvement of var genes in placental adhesion, and considers whether the most appropriate vaccine candidates have yet been identified
The clinical and cost effectiveness of adapted dialectical behaviour therapy (DBT) for bipolar mood instability in primary care (ThrIVe-B programme): a feasibility study
No full textThis is the final version. Available on open access from BMC via the DOI in this recordBACKGROUND: In bipolar spectrum disorder, some individuals experience ongoing, frequent fluctuations in mood outside of affective episodes. There are currently no evidence-based psychological interventions designed to address this. This feasibility study is a phase II evaluation of a dialectical behavioural therapy-informed approach (Therapy for Inter-episode mood Variability in Bipolar [ThrIVe-B]). It seeks to examine the feasibility and acceptability of a future definitive trial evaluating the clinical and cost effectiveness of the ThrIVe-B programme. METHODS/DESIGN: Patients will be randomised 1:1 to either treatment as usual only (control arm) or the ThrIVe-B intervention plus treatment as usual (intervention arm). Follow-up points will be at 3, 6, 9 and 15 months after baseline, with 9 months as the primary end point for the candidate primary outcome measures. We aim to recruit 48 individuals meeting diagnostic criteria for a bipolar spectrum disorder and reporting frequent mood swings outside of acute episodes, through primary and secondary care services and self-referral. To evaluate feasibility and acceptability, we will examine recruitment and retention rates, completion rates for study measures and feedback from participants on their experience of study participation and therapy. DISCUSSION: Proceeding to a definitive trial will be indicated if the following criteria are met: (1) trial participation does not lead to serious negative consequences for our participants; (2) any serious concerns about the acceptability and feasibility of the trial procedures can be rectified prior to a definitive trial; (3) follow-up data at 9 months are available for at least 60% of participants; (4) at least 60% of patients in the ThrIVe-B arm complete treatment. TRIAL REGISTRATION: ISRCTN, ISRCTN54234300 . Registered on 20 July 2017.The trial described by this protocol is funded by the National Institute for Health Research (NIHR) Research for Patient Benefit programme in the UK (grant number PB-PG-1215-20023)
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